The prevention and control of inflammation is of prime importance to the maintenance of human and animal health, and much research has been devoted to development of compounds having anti-inflammatory properties. Certain methods and chemical compositions have been developed which aid in inhibiting or controlling inflammation, but additional anti-inflammatory methods and compositions are needed.
Also of great importance to the maintenance of good health is the control of pathological cellular proliferation such as that which occurs in the case of cancer. Considerable research and resources have been devoted to oncology and antitumor measures including chemotherapy. While certain methods and chemical compositions have been developed which aid in inhibiting, remitting, or controlling the growth of, for example, tumors, new methods and anti-cancer compositions are needed.
A further area of great significance in human and animal health care is immunomodulation. Immunomodulator compounds and compositions, are useful for modulating or regulating immunological functions in animals. Immunomodulators may be immunostimulants for building up immunities to, or initiate healing from, certain diseases and disorders. Conversely, immunomodulators may be immunoinhibitors or immunosuppressors for preventing undesirable immune reactions of the body to foreign materials, or to prevent or ameliorate autoimmune reactions or diseases.
Immunomodulators have been found to be useful for treating systemic autoimmune diseases, such as lupus erythematosus and diabetes, as well as immunodeficiency diseases. Further, immunomodulators may be useful for immunotherapy of cancer or to prevent rejections of foreign organs or other tissues in transplants, e.g., kidney, heart, or bone marrow.
Various immunomodulator compounds have been discovered, including FK506, muramylic acid dipeptide derivatives, levamisole, niridazole, oxysuran, flagyl, interferons, interleukins, leukotrienes, corticosteroids, and cyclosporins. Many of these compounds have been found, however, to have undesirable side effects and/or high toxicity. New immunomodulator compounds are therefore needed to provide a wider range of immunomodulator function for specific areas with a minimum of undesirable side effects.
It has been found that some natural products and organisms are potential sources for chemical molecules having useful biological activities. Marine sponges have proved to be such a source, and a number of publications have issued disclosing organic compounds derived from marine sponges. Such publications include Scheuer, P. J., Ed. (1978-1983) Marine Natural Products, Chemical and Biological Perspectives, Academic Press, New York; Faulkner,D. (1998)J. Nat. Prod. Rep. 15:113-158;(1997)J. Nat. Prod. Rep. 14:259-302; (1996)J. Nat. Prod. Rep. 13:75-125; (1995)J. Nat. Prod. Rep. 12:223-269; (1994)J. Nat. Prod. Rep. 11:355-394;(1993)J. Nat. Prod. Rep. 10:497-539;(1992)J. Nat. Prod. Rep. 9:323-364; (1991)J. Nat. Prod. Rep. 8:97-147; (1990)J. Nat. Prod. Rep. 7:269-309; (1988) J. Nat. Prod. Rep. 5:613-663; (1987)J. Nat. Prod. Rep. 4:539-576;(1986)J. Nat. Prod. Rep. 3:1-33;(1984)J. Nat. Prod. Rep. 1:551-598;and Uemura, D., K. Takahashi, T. Yamamoto, C. Katayama, J. Tanaka, Y. Okumura, Y. Hirata (1985) J. Am. Chem. Soc. 107:4796-4798.
Utilizing sponges as a source material and supplemented by novel synthetic production methods, new classes of biologically active compounds and new pharmaceutical compositions have been provided to the art. However, as noted above, there is a great need for additional compounds useful in treating a variety of pathological conditions.